Induction of apoptosis by fumonisin B1 in HT29 cells is mediated by the accumulation of endogenous free sphingoid bases.
Fumonisin B1 (FB1) and aminopentol (AP1) (which is formed by hydrolysis of FB1) are found in corn contaminated with some strains of Fusarium moniliforme. Incubation of HT29 cells (a human colonic cell line) with FB1 or AP1 caused a significant reduction in cell number; AP1 was less potent, with 50 microM AP1 causing the same reduction (ca. 30% after 24 h) as 10 microM FB1. The reduction in cell number reflected increases in DNA fragmentation and the percentage of apoptotic cells. Both FB1 and AP1 caused the accumulation of sphinganine (25- and 35-fold by 10 microM FB1 and 50 microM AP1, respectively); thus, concentrations of FB1 and AP1 that caused comparable reductions in cell number were also similar with respect to elevation of sphinganine, a compound that is growth inhibitory and cytotoxic. Inhibition of the first step of sphingolipid biosynthesis with ISP-1 prevented the elevation in sphinganine, DNA fragmentation, and apoptosis induced by FB1. Therefore, these effects of FB1 on HT29 cells can be attributed to the accumulation of sphinganine. Since consumption of food contaminated with Fusarium moniliforme (Sheldon) exposes colonic cells to these mycotoxins, the possibility that FB1 and AP1 are toxic for intestinal cells in vivo should be evaluated, especially in the light of the recent report (Bhat et al., Clin. Toxicol. 35, 249, 1997) describing intestinal disturbances in humans after consumption of moldy corn and sorghum containing fumonisins.
Schmelz
E M
EM
Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322-3050, USA. eschmel@emory.edu
Dombrink-Kurtzman
M A
MA
Roberts
P C
PC
Kozutsumi
Y
Y
Kawasaki
T
T
Merrill
A H
AH
D000935:Antifungal Agents / Q000494:pharmacology; D017209:Apoptosis; D002264:Carboxylic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002452:Cell Count / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D005506:Food Contamination; D037341:Fumonisins; D019073:HT29 Cells / Q000187:drug effects*; D006801:Humans; D009183:Mycotoxins / Q000633:toxicity*; D013107:Sphingolipids / Q000032:analysis / Q000096:biosynthesis; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D003313:Zea mays
D000935:Antifungal Agents; D002264:Carboxylic Acids; D002274:Carcinogens, Environmental; D004791:Enzyme Inhibitors; D005229:Fatty Acids, Monounsaturated; D037341:Fumonisins; D009183:Mycotoxins; D013107:Sphingolipids; C110744:aminopentol; C056933:fumonisin B1; D013110:Sphingosine; C005682:safingol; C001996:thermozymocidin